National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)

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ClinicalTrials.gov Identifier: NCT01322165

Recruitment Status : Completed

First Posted : March 24, 2011

Last Update Posted : December 20, 2016

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Sponsor:

Collaborator:

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Information provided by (Responsible Party):

National Heart, Lung, and Blood Institute (NHLBI)

Study Description

Brief Summary:

The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) was initiated in 2006 by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). GenTAC established a registry of 3706 patients with genetic conditions that may be related to thoracic aortic aneurysms and collected medical data and biologic samples. The study ended in September 2016. Data and samples are available from NHLBI and requests should be made to BioLINCC. See the NHLBI website for more information: https://www.nhlbi.nih.gov/research/resources/gentac/.

Condition or disease
Marfan Syndrome Turner Syndrome Ehlers-Danlos Syndrome Loeys-Dietz Syndrome FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation Bicuspid Aortic Valve Without Known Family History Bicuspid Aortic Valve With Family History Bicuspid Aortic Valve With Coarctation Familial Thoracic Aortic Aneurysm and Dissections Shprintzen-Goldberg Syndrome Other Aneur/Diss of Thoracic Aorta Not Due to Trauma, <50yo Other Congenital Heart Disease

Condition or disease

Marfan Syndrome Turner Syndrome Ehlers-Danlos Syndrome Loeys-Dietz Syndrome FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation Bicuspid Aortic Valve Without Known Family History Bicuspid Aortic Valve With Family History Bicuspid Aortic Valve With Coarctation Familial Thoracic Aortic Aneurysm and Dissections Shprintzen-Goldberg Syndrome Other Aneur/Diss of Thoracic Aorta Not Due to Trauma, <50yo Other Congenital Heart Disease

Study Design

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Study Type :	Observational
Actual Enrollment :	3706 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
Study Start Date :	November 2007
Actual Primary Completion Date :	September 2015
Actual Study Completion Date :	September 2016

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Turner syndrome Marfan syndrome Loeys-Dietz syndrome Ehlers-Danlos syndrome Familial thoracic aortic aneurysm and dissection Shprintzen-Goldberg syndrome

MedlinePlus related topics: Aneurysms Aortic Aneurysm

Genetic and Rare Diseases Information Center resources: Ehlers-Danlos Syndromes Marfan Syndrome Turner Syndrome Gonadal Dysgenesis Aortic Coarctation Loeys-Dietz Syndrome Galactosialidosis Familial Thoracic Aortic Aneurysm and Aortic Dissection Shprintzen-Goldberg Craniosynostosis Syndrome

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

Thoracic aortic aneurysms and dissections and their associated surgical interventions [ Time Frame: bi-annual ]

Biospecimen Retention: Samples With DNA

If a blood specimen is obtained, it is separated and stored as plasma, viable cells, and extracted DNA. If a saliva specimen is obtained, it is stored for DNA.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

The cohort consists of patients with conditions related to genetically-induced thoracic aortic aneurysms.

Criteria

Eligible subjects must have one of the conditions listed below and be enrolled in-person at one of the participating clinical centers.Contact the study coordinator at the location nearest you for more information about participation.

Marfan syndrome
Turner syndrome
Ehlers-Danlos syndrome
Loeys-Dietz syndrome
FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 genetic mutation
Bicuspid aortic valve without known family history
Bicuspid aortic valve with family history
Bicuspid aortic valve with coarctation
Familial Thoracic Aortic Aneurysm and DissectionsYes
Shprintzen-Goldberg syndrome
Other aneurysms and dissections of the thoracic aorta not due to trauma, <50yo
Other congenital heart disease (e.g., Tetralogy of Fallot, coarctation)

Exclusion Criteria:

Inability of the patient, parent or guardian to give consent.
Unwillingness to provide a blood or buccal specimen.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01322165

Locations

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United States, Hawaii
Queens Medical Center
Honolulu, Hawaii, United States, 96813
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, New York
The New York Presbyterian Hospital-Weill Cornell Medical Center
New York, New York, United States, 10021
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Medical School at Houston
Houston, Texas, United States, 77030

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

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Study Director:	Barbara Kroner, PhD, MPH	RTI International
Principal Investigator:	Richard Devereux, MD	The New York Presbyterian Hospital-Weill Cornell Medical Center
Principal Investigator:	William Ravekes, M.D.	Johns Hopkins University
Principal Investigator:	Reed E. Pyeritz, M.D., Ph.D.	University of Pennsylvania
Principal Investigator:	Dianna M. Milewicz, M.D. Ph.D.	University of Texas Medical School at Houston
Principal Investigator:	Scott A. LeMaire, M.D.	Baylor College of Medicine
Principal Investigator:	Cheryl L. Maslen, Ph.D.	Oregon Health and Science University
Principal Investigator:	Ralph Shohet, MD	University of Hawaii
Principal Investigator:	Jennifer Habashi, MD	Johns Hopkins University
Principal Investigator:	Federico M. Asch, MD,FACC,FASE	Medstar
Study Chair:	Kim Eagle, M.D.	University of Michigan

More Information

Additional Information:

GenTAC project resources being maintained by NHLBI since contract end. This link exits the ClinicalTrials.gov site

Publications of Results:

Song HK, Bavaria JE, Kindem MW, Holmes KW, Milewicz DM, Maslen CL, Pyeritz RE, Basson CT, Eagle K, Tolunay HE, Kroner BL, Dietz H, Menashe V, Devereux RB, Desvigne-Nickens P, Ravekes W, Weinsaft JW, Brambilla D, Stylianou MP, Hendershot T, Mitchell MS, LeMaire SA; National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) Consortium. Surgical treatment of patients enrolled in the national registry of genetically triggered thoracic aortic conditions. Ann Thorac Surg. 2009 Sep;88(3):781-7; discussion 787-8. doi: 10.1016/j.athoracsur.2009.04.034.

Kroner BL, Tolunay HE, Basson CT, Pyeritz RE, Holmes KW, Maslen CL, Milewicz DM, LeMaire SA, Hendershot T, Desvigne-Nickens P, Devereux RB, Dietz HC, Song HK, Ringer D, Mitchell M, Weinsaft JW, Ravekes W, Menashe V, Eagle KA. The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC): results from phase I and scientific opportunities in phase II. Am Heart J. 2011 Oct;162(4):627-632.e1. doi: 10.1016/j.ahj.2011.07.002.

Song HK, Kindem M, Bavaria JE, Dietz HC, Milewicz DM, Devereux RB, Eagle KA, Maslen CL, Kroner BL, Pyeritz RE, Holmes KW, Weinsaft JW, Menashe V, Ravekes W, LeMaire SA; Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Consortium. Long-term implications of emergency versus elective proximal aortic surgery in patients with Marfan syndrome in the Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Consortium Registry. J Thorac Cardiovasc Surg. 2012 Feb;143(2):282-6. doi: 10.1016/j.jtcvs.2011.10.024. Epub 2011 Nov 20.

Holmes KW, Maslen CL, Kindem M, Kroner BL, Song HK, Ravekes W, Dietz HC, Weinsaft JW, Roman MJ, Devereux RB, Pyeritz RE, Bavaria J, Milewski K, Milewicz D, LeMaire SA, Hendershot T, Eagle KA, Tolunay HE, Desvigne-Nickens P, Silberbach M; GenTAC Registry Consortium. GenTAC registry report: gender differences among individuals with genetically triggered thoracic aortic aneurysm and dissection. Am J Med Genet A. 2013 Apr;161A(4):779-86. doi: 10.1002/ajmg.a.35836. Epub 2013 Feb 26.

Other Publications:

Eagle KA; GenTAC Consortium. Rationale and design of the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Am Heart J. 2009 Feb;157(2):319-26. doi: 10.1016/j.ahj.2008.10.005. Epub 2008 Dec 17.

Matt P, Schoenhoff F, Habashi J, Holm T, Van Erp C, Loch D, Carlson OD, Griswold BF, Fu Q, De Backer J, Loeys B, Huso DL, McDonnell NB, Van Eyk JE, Dietz HC; GenTAC Consortium. Circulating transforming growth factor-beta in Marfan syndrome. Circulation. 2009 Aug 11;120(6):526-32. doi: 10.1161/CIRCULATIONAHA.108.841981. Epub 2009 Jul 27.

Kuang SQ, Guo DC, Prakash SK, McDonald ML, Johnson RJ, Wang M, Regalado ES, Russell L, Cao JM, Kwartler C, Fraivillig K, Coselli JS, Safi HJ, Estrera AL, Leal SM, LeMaire SA, Belmont JW, Milewicz DM; GenTAC Investigators. Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections. PLoS Genet. 2011 Jun;7(6):e1002118. doi: 10.1371/journal.pgen.1002118. Epub 2011 Jun 16.

Mendoza DD, Kochar M, Devereux RB, Basson CT, Min JK, Holmes K, Dietz HC, Milewicz DM, LeMaire SA, Pyeritz RE, Bavaria JE, Maslen CL, Song H, Kroner BL, Eagle KA, Weinsaft JW; GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Study Investigators. Impact of image analysis methodology on diagnostic and surgical classification of patients with thoracic aortic aneurysms. Ann Thorac Surg. 2011 Sep;92(3):904-12. doi: 10.1016/j.athoracsur.2011.03.130. Epub 2011 Jul 2.

LeMaire SA, McDonald ML, Guo DC, Russell L, Miller CC 3rd, Johnson RJ, Bekheirnia MR, Franco LM, Nguyen M, Pyeritz RE, Bavaria JE, Devereux R, Maslen C, Holmes KW, Eagle K, Body SC, Seidman C, Seidman JG, Isselbacher EM, Bray M, Coselli JS, Estrera AL, Safi HJ, Belmont JW, Leal SM, Milewicz DM. Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet. 2011 Sep 11;43(10):996-1000. doi: 10.1038/ng.934.

Guo DC, Regalado E, Casteel DE, Santos-Cortez RL, Gong L, Kim JJ, Dyack S, Horne SG, Chang G, Jondeau G, Boileau C, Coselli JS, Li Z, Leal SM, Shendure J, Rieder MJ, Bamshad MJ, Nickerson DA; GenTAC Registry Consortium; National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project; Kim C, Milewicz DM. Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet. 2013 Aug 8;93(2):398-404. doi: 10.1016/j.ajhg.2013.06.019. Epub 2013 Aug 1.

Prakash S, Guo D, Maslen CL, Silberbach M, Milewicz D, Bondy CA; GenTAC Investigators. Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome. Genet Med. 2014 Jan;16(1):53-9. doi: 10.1038/gim.2013.77. Epub 2013 Jun 6. Erratum In: Genet Med. 2014 Jan;16(1):117.

Cook JR, Carta L, Benard L, Chemaly ER, Chiu E, Rao SK, Hampton TG, Yurchenco P; GenTAC Registry Consortium; Costa KD, Hajjar RJ, Ramirez F. Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. J Clin Invest. 2014 Mar;124(3):1329-39. doi: 10.1172/JCI71059. Epub 2014 Feb 17.

Song HK, Preiss LR, Maslen CL, Kroner B, Devereux RB, Roman MJ, Holmes KW, Tolunay HE, Desvigne-Nickens P, Asch FM, Milewski RK, Bavaria J, LeMaire SA; GenTAC Consortium. Valve-sparing aortic root replacement in patients with Marfan syndrome enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions. J Heart Valve Dis. 2014 May;23(3):292-8.

Doyle JJ, Doyle AJ, Wilson NK, Habashi JP, Bedja D, Whitworth RE, Lindsay ME, Schoenhoff F, Myers L, Huso N, Bachir S, Squires O, Rusholme B, Ehsan H, Huso D, Thomas CJ, Caulfield MJ, Van Eyk JE, Judge DP, Dietz HC; GenTAC Registry Consortium; MIBAVA Leducq Consortium. A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome. Elife. 2015 Oct 27;4:e08648. doi: 10.7554/eLife.08648.

Asch FM, Yuriditsky E, Prakash SK, Roman MJ, Weinsaft JW, Weissman G, Weigold WG, Morris SA, Ravekes WJ, Holmes KW, Silberbach M, Milewski RK, Kroner BL, Whitworth R, Eagle KA, Devereux RB, Weissman NJ; GenTAC Investigators. The Need for Standardized Methods for Measuring the Aorta: Multimodality Core Lab Experience From the GenTAC Registry. JACC Cardiovasc Imaging. 2016 Mar;9(3):219-26. doi: 10.1016/j.jcmg.2015.06.023. Epub 2016 Feb 17.

Guo DC, Gong L, Regalado ES, Santos-Cortez RL, Zhao R, Cai B, Veeraraghavan S, Prakash SK, Johnson RJ, Muilenburg A, Willing M, Jondeau G, Boileau C, Pannu H, Moran R, Debacker J; GenTAC Investigators, National Heart, Lung, and Blood Institute Go Exome Sequencing Project; Montalcino Aortic Consortium; Bamshad MJ, Shendure J, Nickerson DA, Leal SM, Raman CS, Swindell EC, Milewicz DM. MAT2A mutations predispose individuals to thoracic aortic aneurysms. Am J Hum Genet. 2015 Jan 8;96(1):170-7. doi: 10.1016/j.ajhg.2014.11.015. Epub 2014 Dec 31.

Kuang SQ, Medina-Martinez O, Guo DC, Gong L, Regalado ES, Reynolds CL, Boileau C, Jondeau G, Prakash SK, Kwartler CS, Zhu LY, Peters AM, Duan XY, Bamshad MJ, Shendure J, Nickerson DA, Santos-Cortez RL, Dong X, Leal SM, Majesky MW, Swindell EC, Jamrich M, Milewicz DM. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest. 2016 Mar 1;126(3):948-61. doi: 10.1172/JCI83778. Epub 2016 Feb 8.

Prakash S, Kuang SQ; GenTAC Registry Investigators; Regalado E, Guo D, Milewicz D. Recurrent Rare Genomic Copy Number Variants and Bicuspid Aortic Valve Are Enriched in Early Onset Thoracic Aortic Aneurysms and Dissections. PLoS One. 2016 Apr 19;11(4):e0153543. doi: 10.1371/journal.pone.0153543. eCollection 2016.

Weinsaft JW, Devereux RB, Preiss LR, Feher A, Roman MJ, Basson CT, Geevarghese A, Ravekes W, Dietz HC, Holmes K, Habashi J, Pyeritz RE, Bavaria J, Milewski K, LeMaire SA, Morris S, Milewicz DM, Prakash S, Maslen C, Song HK, Silberbach GM, Shohet RV, McDonnell N, Hendershot T, Eagle KA, Asch FM; GENTAC Registry Investigators. Aortic Dissection in Patients With Genetically Mediated Aneurysms: Incidence and Predictors in the GenTAC Registry. J Am Coll Cardiol. 2016 Jun 14;67(23):2744-2754. doi: 10.1016/j.jacc.2016.03.570.

Roman MJ, Pugh NL, Hendershot TP, Devereux RB, Dietz H, Holmes K, Eagle KA, LeMaire SA, Milewicz DM, Morris SA, Pyeritz RE, Ravekes WJ, Shohet RV, Silberbach M; GenTAC InvestigatorsDietzHarry C.HabashiJenniferPrakashSiddharth K.MaslenCheryl L.SongHoward K.BavariaJoseph E.MilewskiKariannaWeinsaftJonathan W.McDonnellNazliAschFederico M.TolunayH. EserDesvigne-NickensPatriceTsengHungKronerBarbara L. Aortic Complications Associated With Pregnancy in Marfan Syndrome: The NHLBI National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). J Am Heart Assoc. 2016 Aug 11;5(8):e004052. doi: 10.1161/JAHA.116.004052.

Prakash SK, Bondy CA, Maslen CL, Silberbach M, Lin AE, Perrone L, Limongelli G, Michelena HI, Bossone E, Citro R; BAVCon Investigators, GenTAC Registry Investigators; Lemaire SA, Body SC, Milewicz DM. Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry. Am J Med Genet A. 2016 Dec;170(12):3157-3164. doi: 10.1002/ajmg.a.37953. Epub 2016 Sep 8.

Guo DC, Grove ML, Prakash SK, Eriksson P, Hostetler EM, LeMaire SA, Body SC, Shalhub S, Estrera AL, Safi HJ, Regalado ES, Zhou W, Mathis MR; GenTAC Investigators; BAVCon Investigators; Eagle KA, Yang B, Willer CJ, Boerwinkle E, Milewicz DM. Genetic Variants in LRP1 and ULK4 Are Associated with Acute Aortic Dissections. Am J Hum Genet. 2016 Sep 1;99(3):762-769. doi: 10.1016/j.ajhg.2016.06.034. Epub 2016 Aug 25.

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Responsible Party:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT01322165
Other Study ID Numbers:	1438 268201000048C-5-0-1 ( U.S. NIH Grant/Contract ) N01HV68199-7-0-1 ( U.S. NIH Grant/Contract )
First Posted:	March 24, 2011 Key Record Dates
Last Update Posted:	December 20, 2016
Last Verified:	December 2016

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):


Marfan syndrome Turner syndrome Bicuspid aortic valve Ehlers-Danlos Syndrome Loeys-Dietz syndrome Aneurysm	Genetic aortic thoracic mutation dissection

Additional relevant MeSH terms:

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Marfan Syndrome Arachnodactyly Loeys-Dietz Syndrome Turner Syndrome Gonadal Dysgenesis Heart Diseases Aneurysm, Dissecting Aneurysm Aortic Aneurysm Heart Defects, Congenital Ehlers-Danlos Syndrome Bicuspid Aortic Valve Disease Aortic Aneurysm, Thoracic Heart Valve Diseases Syndrome	Disease Pathologic Processes Cardiovascular Diseases Vascular Diseases Aortic Diseases Cardiovascular Abnormalities Congenital Abnormalities Disorders of Sex Development Urogenital Abnormalities Sex Chromosome Disorders of Sex Development Sex Chromosome Disorders Chromosome Disorders Genetic Diseases, Inborn Gonadal Disorders Endocrine System Diseases

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